Prospective Clinical Trials Research Articles

PCDH11X mutation as a potential biomarker for immune checkpoint therapies in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have achieved impressive success in lung adenocarcinoma (LUAD). However, the response to ICIs varies among patients, and predictive biomarkers are urgently needed. PCDH11X is frequently mutated in LUAD, while its role in ICI treatment is unclear. In this study, we curated genomic and clinical data of 151 LUAD patients receiving ICIs from three independent cohorts. Relations between PCDH11X and treatment outcomes of ICIs were examined. A melanoma cohort collected from five published studies, a pan-cancer cohort, and non-ICI-treated TCGA-LUAD cohort were also examined to investigate whether PCDH11X mutation is a specific predictive biomarker for LUAD ICI treatment. Among the three ICI-treated LUAD cohorts, PCDH11X mutation (PCDH11X-MUT) was associated with better clinical response compared to wild-type PCDH11X (PCDH11X-WT). While in ICI-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and the non-ICI-treated TCGA-LUAD cohort, no significant differences in overall survival (OS) were observed between the PCDH11X-MUT and PCDH11X-WT groups. PCDH11X mutation was associated with increased PD-L1 expression, tumor mutation burden (TMB), neoantigen load, DNA damage repair (DDR) mutations, and hot tumor microenvironment in TCGA-LUAD cohort. Our findings suggested that the PCDH11X mutation might serve as a specific biomarker to predict the efficacy of ICIs for LUAD patients. Considering the relatively small sample size of ICI-treated cohorts, future research with larger cohorts and prospective clinical trials will be essential for validating and further exploring the role of PCDH11X mutation in the context of immunotherapy outcomes in LUAD. KEY MESSAGES: PCDH11X mutation is associated with better clinical response compared to wild type PCDH11X in three ICIs-treated LUAD cohorts. In ICIs-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and non-ICIs-treated TCGA-LUAD cohortsPCDH11X mutation is not associated with better clinical response, suggesting PCDH11X mutation might be a specific biomarker to predict the efficacy of ICIs treatment for LUAD patients. PCDH11X mutation is associated with increased PD-L1 expression, tumor mutation burden, and neoantigen load in TCGA-LUAD cohort. PCDH11X mutation is associated with hot tumor microenvironment in TCGA-LUAD cohort.

Prostate-Specific Membrane Antigen Positron Emission Tomography Oncological Applications beyond Prostate Cancer in Comparison to Other Radiopharmaceuticals.

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (68Ga) or fluoro-18 (18F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [18F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. We performed a bibliographic search on three different databases until February 2024 using the following terms: "positron emission tomography", "PET", "PET/CT", "Prostate-specific membrane antigen", "PSMA", "non-prostate", "not prostate cancer", "solid tumor", "FDG", "Fluorodeoxyglucose", "FAPi", "FET", "MET", "DOPA", "choline", "FCH", "FES", "DOTATOC", "DOTANOC", and "DOTATATE". Only original articles edited in English with at least 10 patients were included. Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [18F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [18F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications.

Challenges during pancreatoduodenectomy and ways to overcome them

Background. Pancreaticoduodenal resection (PDR) is the surgical procedure for cancer of the head of the pancreas, distal common bile duct, duodenum and ampulla of Vater. This surgery is associated with a high risk of complications, the development of which can be influenced by various factors. since pancreatic fistula is a key complication of PDR, the choice of the method for pancreatic anastomosis becomes especially important. Material and methods. The search for publications was carried out using the PubMed and Elibrary systems from January 1980 to January 2024. of the 2,300 sources found, 69 were used to write the review. We included data from both retrospective and prospective clinical trials that were devoted to pancreatoduodenectomy for malignant neoplasms, the difficulties encountered in performing this surgery and ways to solve them. Results. Currently, there are more than 60 types of pancreatico-digestive anastomosis, which indirectly indicates the absence of a universal one that ensures the prevention of pancreatic fistula. The treatment outcomes may be influenced by the nature of neoadjuvant treatment, concomitant diseases, anatomical features, presence of obstructive jaundice and methods of its relief. The main mechanisms of influence of negative factors on the development of complications are considered. an individual approach to the patient, taking into account all factors, can significantly reduce the risk of complications.

Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Local procedures for axillary hyperhidrosis and osmidrosis: A systematic review of prospective and controlled clinical trials

AbstractAxillary hyperhidrosis and osmidrosis are challenging to treat, and neither topical nor systemic drugs have provided optimal treatment outcomes. In the past decades, treatment with botulinum toxin (BTX) has gained status as the gold standard, but it has its limitations both in regard to duration as well as indication for osmidrosis, specifically. A variety of local interventions have been explored in both the surgical field and within energy‐based devices (EBDs) for alternative in‐office treatments, but a collective overview is lacking. This study sought to investigate and assess the evidence on and effect of current local procedures for axillary hyperhidrosis and osmidrosis. A systematic search for prospective and controlled clinical trials in the databases PubMed, Embase and Cochrane Library until 31 December 2023 was executed. Relevant literature was identified independently by two authors according to predefined inclusion and exclusion criteria. Fifty‐nine studies met the criteria for final inclusion, of which 46 studies were randomized controlled trials and 13 were nonrandomized trials. The included studies were classified by procedure type. Individually, a total of 28 studies investigated BTXs, 11 studies explored EBDs, while six studies reported on surgical interventions. Additionally, 14 studies evaluated alternative procedures or investigated combinations and side‐by‐side comparisons of the different procedure types. The dominant evidence on efficacy and safety was of BTX A. EBDs are increasingly being investigated with microwave thermolysis appearing to be the singular most established and scientifically well‐founded method. In the surgical field, less‐invasive methods are gaining ground. To meet the increasing demand for individualized treatment, additional high‐quality comparative studies are required for the establishment of a future variety of standard treatments.

Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix.

Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY-078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once-weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off-label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis

BackgroundWe investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors.MethodsStudy participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan–Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance.ResultsA total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative.ConclusionsAdjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Examining the connection between weekend catch-up sleep and depression: Insights from 2017 to 2020 NHANES information

BackgroundDepression, a prevalent mental disorder, has shown an increasing trend in recent years, imposing a significant burden on health and society. Adequate sleep has been proven to reduce the incidence of depression. This study seeks to explore how Weekend Catch-up Sleep (WCS) is connected with the prevalence of depression in the American population. MethodsThe National Health and Nutrition Examination Survey (NHANES) provides representative data for the U.S. population. We utilized data from the 2017–2018 and 2019–2020 cycles. Depression was operationally defined as a PHQ-9 score exceeding 10. WCS duration was categorized into five groups: no change in sleep duration (=0 h), decreased sleep duration (<0), short catch-up sleep duration (>0 h, ≤1 h), moderate catch-up sleep duration (>1 h, <2 h), and long catch-up sleep duration (≥2 h). ResultsAmong the 8039 individuals, the distribution of WCS duration was as follows: no change (WCS = 0 h) in 2999 individuals (37.3 %), decreased sleep (WCS < 0 h) in 1199 individuals (14.9 %), short catch-up sleep (0 h < WCS ≤ 1 h) in 1602 individuals (19.9 %), moderate catch-up sleep (1 h < WCS < 2 h) in 479 individuals (6.0 %), and long catch-up sleep (WCS ≥ 2 h) in 1760 individuals (21.9 %). Acting by adjustment for all covariates in a multiple regression analysis, we discovered that persons with 1 to 2 h of weekend catch-up sleep had a substantially low prevalence of depression concerning those with WCS = 0 (OR 0.22, 95 % CI 0.08–0.59, P = 0.007). ConclusionThe prevalence of depression in individuals engaging in weekend catch-up sleep for 1 to 2 h is lower than those who do not catch up on weekends. This discovery on the treatment and prevention of depression provides a new perspective. However, further prospective research and clinical trials are needed for a comprehensive investigation.

Abstract PO2-13-04: Single cell characterization of senescent CD8+ T cell promotes immunotherapy resistance in early-stage triple-negative breast cancer

Abstract Background: Immune checkpoint blockade (ICB) has been explored in triple-negative breast cancer (TNBC) and has been proven to improve patient survival in advanced TNBCs (IMpassion130) or increase the pathological complete response rate in early TNBCs (KEYNOTE522). However, ICB could only benefit a subset of patients, highlighting the urgent need to optimize patient selection. Unlike in advanced TNBCs, a predictive biomarker for ICB in early TNBCs is still lacking. The main reason might be that previous studies neglected the heterogeneity of tumor ecosystems between early and advanced TNBCs. There is an urgent need to understand the unique ecosystem of early-stage TNBC and develop biomarkers for precision immunotherapy. Objective: This study aims to characterize the micro-loop associated with the immune efficacy of early TNBC, so as to explain the mechanisms behind the differences in early and late efficacy markers, identify efficacy markers in early TNBC immunotherapy, and search for clinical targeting strategies to sensitize TNBC for neoadjuvant therapy. Methods: We conducted an in-depth analysis of 32 single-cell transcriptomes, comprising 26 early-stage TNBC enrolled in prospective clinical trials (NCT04418154 and NCT04613674), receiving neoadjuvant chemotherapy alone (n=8) or combined with anti-PD1 (n=18), and 6 advanced TNBC. We analyzed the microenvironmental differences between early and advanced tumors, and between different treatment response groups in early stages, and identified a subpopulation of cells specific to early stages and associated with immunotherapeutic efficacy. We used mIHC, flow-through, and validated the presence of this cell in clinical samples. We also explored its predictive performance on four independent cohorts of TNBCs with ICB treatment (GSE194040, NCT04129996, GSE169246, GSE124821). Furthermore, to understand the impact of ISG+ T cells on immunotherapy efficacy and explore targeting strategies, we employed a multi-faceted approach to assess their tumor-killing ability, response to Anti-PD1 treatment, and sensitization effect of drugs targeting ISG+ T cells. ISG+ T cells were sorted using flow cytometry for further experiment. In vitro, we established a co-culture model of primary TNBC patients-derived organoid (PDO) and tumor infiltrated CD8+T cells and evaluated the tumor cell viability as well as T cell cytotoxicity. In vivo, we established TS/A tumor cell bearing BalB/c mouse and E0771 tumor cell-bearing C57BL mouse and measured tumor size and tumor microenvironment by flow cytometry. Results: We obtained 236,017 high-quality cells and identified cell subsets across 32 samples with different stages, treatments and responses. We then uncovered an enriched subset of interferon-induced (ISG+) CD8+ T cells specific to early TNBC, serving as a predictive factor for ICB resistance. Mechanistically, the upregulation of the IFN pathway in early-stage TNBC triggers a transition in ISG+ CD8+ T cells, resulting in cellular senescence, diminished cytotoxicity, and impaired response to ICB. Encouragingly, we made a noteworthy discovery that Nicotinamide mononucleotide, an anti-aging drug, effectively restores the functionality of ISG+ CD8+ T cells, amplifying immunotherapy sensitivity. Conclusions: This study provided a comprehensive single-cell transcriptome atlas of early-stage TNBC and depicted stage-related ISG+CD8+ T cell for predicting ICB response in early TNBC. We emphasize the critical role of T cell dysfunction prompted by cellular senescence in driving ICB resistance during the early stages of TNBC and propose an approach for sensitizing immunotherapy with aging drugs. Citation Format: Tong Fu, Yi-Yu Chen, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. Single cell characterization of senescent CD8+ T cell promotes immunotherapy resistance in early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-04.

Intracytoplasmic Sperm Injection Versus In vitro Fertilization in Infertile Women with Thyroid Autoimmunity.

Background: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared with in vitro fertilization (IVF). Methods: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer (ET) treatment cycle from January 2019 to February 2021. In total, 2171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8702 and 2668women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy, and live birth after the first ET cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. Results: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in the TAI-positive and IVF group vs. 0.7 [0.5-0.8] in the TAI-positive and ICSI group vs. 0.6 [0.5-0.8] theTAI-negative and IVF group vs. 0.7 [0.5-0.8] in the TAI-negativeand ICSI group, p < 0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio [aOR]: 0.80 [confidence interval, CI: 0.67-0.97]; clinical pregnancy: 43.0% vs. 38.8%, aOR: 0.81 [CI: 0.67-0.97]; live birth: 36.2% vs. 32.4%, aOR: 0.81 [CI: 0.66-0.98]). Conclusion: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared with IVF. Further prospective clinical trials are needed to confirm our findings.

Anticytokine Therapy and Corticosteroids for Cytokine Release Syndrome and for Neurotoxicity Following T-Cell Engager or CAR T-Cell Therapy

What Is the Issue? Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common toxicities secondary to T-cell engager or chimeric antigen receptor (CAR) T-cell therapy. The US FDA and Health Canada approved tocilizumab, an anti-interleukin-6 receptor antagonist, for the management of severe or life-threatening cases of CRS. Corticosteroids also play an important role in CRS management and are the mainstay of ICANS management. Decision-makers are interested in understanding the use of anticytokine drugs (i.e., tocilizumab, anakinra, siltuximab) and/or corticosteroids in the management of CRS and ICANS following T-cell engager or CAR T-cell therapy. What Did We Do? We identified and summarized the literature comparing the clinical effectiveness and safety of anticytokine therapy and/or corticosteroids with alternative care or treatment as usual for treating and preventing of CRS and ICANS. We also searched for evidence-based recommendations for the use of anticytokine therapy and/or corticosteroids to treat and prevent CRS and ICANS. A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2019 and February 26, 2024 for CRS; and between January 1, 2019 and March 4, 2024 for ICANS. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? This report presents evidence-based findings on 3 retrospective chart review studies, 2 prospective cohort studies, and 4 consensus guidelines. Limited and low-quality clinical evidence from studies with a high risk of bias suggested that early use of tocilizumab or corticosteroids, or prophylactic use of tocilizumab or anakinra may reduce the risk of a high-grade CRS without a negative impact on neurotoxicity or immunotherapy treatment outcomes. The included guidelines recommend the use of tocilizumab for treatment of higher-grade CRS, or for treatment of grade 1 CRS if symptoms persist for 3 days or more. Corticosteroids could be added in conjunction if there is no improvement or persistent symptoms after tocilizumab therapy. For the management of ICANS in the absence of concurrent CRS, supportive care is the preferred treatment option for grade 1 ICANS, while corticosteroids are recommended for the management of grade 2 to 4 ICANS. In the presence of concurrent CRS, guidelines recommend tocilizumab therapy as per management of CRS, and corticosteroids should be continued until improvement to grade 1. We did not identify any clinical evidence regarding the clinical efficacy and safety of anticytokine therapy and/or corticosteroids for treatment of CRS and ICANS compared with alternative treatment or treatment as usual. We also did not identify any guidelines for the use of prophylactic anticytokine therapy, corticosteroids, or both for the prevention of CRS and ICANS. What Does This Mean? Despite limited and low-quality evidence, the findings suggest some potential benefits of prophylactic or early use of anticytokine therapy and corticosteroids for the management of immunotherapy-related toxicities. Guidelines offer guidance on the management of CRS, ICANS and other less common toxicities related to immunotherapy based on the available low-quality evidence. When using the clinical evidence and recommendations summarized in this report to inform decisions, decision-makers should consider that the evidence is limited and of low quality. To improve the certainty of findings, there is a need for more robust prospective clinical trials with larger sample sizes, and lower risk of bias.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Patients with cancer with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded from many cancer clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data are limited regarding the management of HBV and HCV infections in patients with cancer treated with ICIs. To address this gap, we reviewed the literature on management of HBV and HCV infections in patients with cancer receiving ICIs. We searched MEDLINE and PubMed for all original research articles, case reports, and systematic reviews published in English between Jul 2013 and Jul 2023 on patients with cancer with HBV or HCV infection receiving ICIs. We found 28 studies (three prospective clinical trials, seven retrospective cohort studies, nine retrospective case series, and nine case reports) that evaluated the safety of ICI therapy in patients with HBV infection and cancer. The overall rate of HBV reactivation was 1.4% (38/2799), and no HBV-related deaths were reported. The frequency of HBV reactivation in patients with chronic and past HBV infections was 2% (35/1667) and 0.3% (3/1132), respectively. The risk of HBV reactivation was significantly higher among patients with chronic HBV infection not receiving antiviral prophylaxis than among those receiving antivirals (17% vs 1%, p < 0.05). Based on high-quality evidence, for patients with chronic HBV infection, antiviral prophylaxis is recommended before ICI therapy initiation. For patients with past HBV infection, monitoring and on-demand antiviral treatment are sufficient. We found 11 studies (five clinical trials, five retrospective studies, and one prospective observational study) that evaluated the safety of ICI therapy in patients with HCV infection and cancer. The overall rate of HCV reactivation was 0.5% (2/387), and no HCV-related deaths were reported. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICIs are safe for HCV-infected patients with solid tumors. Chronic HBV or HCV infection should not be considered a contraindication for ICI therapy. Specific risk assessment, monitoring, and management strategies are necessary to reduce the risk of ICI-related liver injury in patients with cancer and chronic HBV or HCV infection.

Efficacy of clear aligner therapy over conventional fixed appliances in controlling orthodontic movement: A systematic review.

The purpose of the current systematic review was to answer the clinical research question "Is Clear Aligner Therapy (CAT) effective in controlling the orthodontic movement?" by bringing together the most up-to-date information about the available evidence for CAT. On January 1, 2023, a search was conducted in PubMed, ERIC, Embase, and CINHAL for any research papers published in the previous 10 years that provided an overview of the PICO questions. Both the titles and abstracts of the selected studies were evaluated independently by two different authors, and if there was any disagreement between the two review authors, a third reviewer was brought in to settle it. Among included studies, three were retrospective non-randomized and two studies were prospective randomized clinical trials. Various authors reported better outcome for fixed orthodontic appliances than for clear aligner treatment (CAT) in relation to mandibular incisor proclination. The mean objective grading system score was better for braces (17) than for CAT (12) with no clinically significant difference, while staging had a significant impact on treatment efficacy. The results of this study suggest that clear aligners may be an effective alternative to traditional braces, but more research is needed to confirm these findings and determine the optimal size of future prospective studies evaluating this treatment.

International Migration and Cardiovascular Health: Unraveling the Disease Burden Among Migrants to North America and Europe.

Europe and North America are the 2largest recipients of international migrants from low-resource regions in the world. Here, large differences in cardiovascular disease (CVD) morbidity and death exist between migrants and the host populations. This review discusses the CVD burden and its most important contributors among the largest migrant groups in Europe and North America as well as the consequences of migration to high-income countries on CVD diagnosis and therapy. The available evidence indicates that migrants in Europe and North America generally have a higher CVD risk compared with the host populations. Cardiometabolic, behavioral, and psychosocial factors are important contributors to their increased CVD risk. However, despite these common denominators, there are important ethnic differences in the propensity to develop CVD that relate to pre- and postmigration factors, such as socioeconomic status, cultural factors, lifestyle, psychosocial stress, access to health care and health care usage. Some of these pre- and postmigration environmental factors may interact with genetic (epigenetics) and microbial factors, which further influence their CVD risk. The limited number of prospective cohorts and clinical trials in migrant populations remains an important culprit for better understanding pathophysiological mechanism driving health differences and for developing ethnic-specific CVD risk prediction and care. Only by improved understanding of the complex interaction among human biology, migration-related factors, and sociocultural determinants of health influencing CVD risk will we be able to mitigate these differences and truly make inclusive personalized treatment possible.

Long‐term quality of life after open and laparoscopic total gastrectomy for stage I gastric cancer: A prospective multi‐institutional study (CCOG1504)

AbstractBackgroundLittle information is available from prospective clinical trials on the influences of surgical approaches on postoperative quality of life (QOL). We aimed to prospectively compare chronological changes in postoperative body weight and QOL between laparoscopic and open total gastrectomy for stage I gastric cancer (GC).MethodsWe conducted a multi‐institutional prospective study (CCOG1504) of patients who undergo laparoscopic or open total gastrectomy. Body weight was measured at the baseline and at the 1st, 2nd, and 3rd postoperative years (POY). QOL using the European Organization for Research and Treatment of Cancer quality of life questionnaire‐C30 (EORTC QLQ‐C30) and the Post‐Gastrectomy Syndrome Assessment Scale‐37 (PGSAS‐37) questionnaires were measured at the baseline and at the 1st, 3rd, 6th, 12th, and 36th postoperative months (POM).ResultsWe enrolled 84 patients from 15 institutions, and finally 43 patients for the laparoscopic group and 16 for the open group were eligible for data analysis. There were no significant differences in body weight change between the two groups. The role functioning score among the EORTC QLQ‐C30 tended to be higher (i.e., better QOL) in the laparoscopic group at POM 1 and 12 after surgery compared to the open group. The dissatisfaction at working score among the PGSAS‐37 at 1 month after surgery was lower (i.e. better QOL) in the laparoscopic group compared to the open group.ConclusionsThe results of CCOG1504 indicated that laparoscopic approach for total gastrectomy was associated with a more favorable dissatisfaction at working score (PGSAS‐37).

Treatment at relapse for synovial sarcoma of children and adolescents: A multi-institutional European retrospective analysis.

Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. The study included 41 patients<21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.

Is time really brain in stroke therapy?: A meta-analysis of mechanical thrombectomy up to 155h post ictus.

Mechanicalthrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24h). PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

Analysis of the Prognostic Factors That Influence the Outcome of Periapical Surgery, including Biomimetic Membranes for Tissue Regeneration: A Review.

The objective of this study was to analyze the prognostic factors that influence the outcome of periapical surgery. A systematic search of the literature was carried out using PubMed and Scopus databases between January 2000 and December 2023 with no language limitations. The PICO question of the present systematic review was: What prognostic factors may influence the outcome of periapical surgery? The most relevant randomized controlled clinical trials (RCTs), prospective clinical trials, retrospective studies, and meta-analyses (n = 44) were selected from 134 articles. The reviewed literature evidenced that bone-lesion healing could significantly be improved by the absence of deep periodontal pockets (>4 mm), localization in anterior teeth, the absence of pain and/or preoperative symptoms, a size of bone lesion < 5 mm, the use of ultrasound, the correct placement of retrograde filling material, and the use of different biomimetic membranes for guided tissue regeneration (GTR). Some preoperative and intraoperative factors could significantly improve the prognosis of periapical surgery. However, these results were not conclusive, and further high-quality research is required.